Disorders of White Blood Cells 2024.PDF

Disorders of White Blood Cells White cells & leucopoiesis Changes of WBC in disease Neoplastic disorders of WBC Learning outcomes To demonstrate knowledge on white cells and leucopoiesis To understand changes of WBCs in disease To describe major neoplastic disorders in WBCs Disorders of White Blood...

Disorders of White Blood Cells White cells & leucopoiesis Changes of WBC in disease Neoplastic disorders of WBC Learning outcomes To demonstrate knowledge on white cells and leucopoiesis To understand changes of WBCs in disease To describe major neoplastic disorders in WBCs Disorders of White Blood Cells White cells & leucopoiesis Changes of WBC in disease Neoplastic disorders of WBC Leucocytes Nucleated cells of the peripheral blood, 5 varieties: − neutrophils (granulocytes) − eosinophils (granulocytes) − basophils (granulocytes) − lymphocytes − monocytes Primary function: Against infection or infestation Granulocytes and monocytes: phagocytic Lymphocytes: immune response (eg cell-mediated, Ab) Normal white cell values Differential Leucocytes total Neutrophils Monocytes Basophils Eosinophils Lymphocytes Platelets Absolute (109/l) 4.0 -11 45-75% 2-8 % 0.4 -1% 1- 4% 20 - 40% 2.8 - 7.5 0.2 - 0.8 0.01 - 0.1 0.04 - 0.4 1.5 - 3.5 150 - 400 Leucopoiesis Myeloid S C (stem cells) Lymphoid S C Colony-forming units Pre-T, Pre-B (Granulo-N,Eo,baso, Mono) Myeloblast Monoblast Lymphoblast Monocyte Lymphocytes Committed SC Earliest recognisable precursor Band Cell Granulocytes Neutro-, Eosino-, Basophils T & B cells Mature cell Blood Film- Neutrophil, Lymphocyte Blood Film -Eosinophil Blood Film -Basophil Blood Film -Monocyte Disorders of White Blood Cells White cells & leucopoiesis Changes of WBC in disease Neoplastic disorders of WBC Disorders of white cells - changes in leucocyte counts Leucocytosis: ↑ total numbers Leucopenia: ↓ total numbers Leukaemia: neoplasia of leucopoietic tissue with a massive ↑ total numbers Leukaemoid reaction: massive leucocytosis & immature cells (chronic infections, severe haemolysis) Diagnostic value of leucocyte changes Neutrophil leucocytosis: bacterial infections, tissue damage Lymphocytosis: viral infection Eosinophilia: parasitic infestation / allergy Monocytosis: chronic bacterial infection (TB), malignant neoplasms Basophil leucocytosis: (uncommon) myeloproliferative disorders Neutrophilia (neutrophil leucocytosis) - neutrophils >7.5x109/L (Normal: 2.8-7.5x109/L) normal neutrophilia Causes of neutrophilia Bacterial infections Inflammation/tissue necrosis Metabolic disorders Malignant neoplasia Myeloproliferative disease Drugs (steroids) Physiological (pregnancy, exercise) Neutropenia, < 1.5x109/L (Normal: 2.8-7.5x109/L) Causes of neutropenia Selective neutropenia: Viral infection Severe bacterial infection, e.g. typhoid Drug induced: e.g. anti-inflammatory agents Autoimmune: e.g. rheumatoid arthritis As part of pancytopenia: Bone marrow failure & infiltration - cytotoxic drug therapy; irradiation; malignant infiltration Severe megaloblastic anaemia (impaired DNA synthesis) Hypersplenism Clinical features Infections, more frequent and serious Severe neutropenia (5x10 ) Normal: 1.5 - 3.5x109/L Causes of lymphocytosis: Acute, viral infections: e.g. infectious mononucleosis; can be extreme in children Chronic infections: e.g. tuberculosis Leukaemia: chronic lymphocytic leukaemia (CLL); acute lymphoblastic leukaemia (ALL) Non Hodgkin’s lymphoma Clinical feature: Lymphadenopathy Disorders of White Blood Cells White cells & leucopoiesis Changes of WBC in disease Neoplastic disorders of WBC Neoplastic disorders of WBC Malignancies of myeloid and lymphoid systems: leukaemias & lymphomas. Leukaemia: occurring predominantly in bone marrow & circulating blood Lymphoma: in lymphoid tissue; tissue mass is a presenting feature Leukaemias and lymphomas may co-exist. Pathogenesis of WBC neoplasm At least one or more molecular abnormalities: chromosomal abnormalities detected in leukaemias and lymphomas; Clonal proliferation of one cell type Neoplastic cells taking over bone marrow or lymphoid tissue Leukaemias (L) Incidence − 10/100,000 per year Neoplastic monoclonal proliferation of WBC precursors Common features: − Replacement of normal bone marrow by leukaemic cells; variable accumulation of abnormal cells in peripheral blood − Infiltration of organs by leukaemic cells (liver, spleen, lymph nodes, meninges, gonads) Most important consequence: − Bone marrow failure (anaemia, neutropenia, thrombocytopenia) Classification of leukaemia Classified as being acute / chronic, and of myeloid / lymphoid origin Acute (A): about 50% of all leukaemia (L) − Myeloblastic (AML): All age groups; incidence ↑ with age; FAB (French-American-British) classification: M0-M7 − Lymphoblastic (ALL): Mostly in children; FAB: L1-L3 Chronic (C): about 45% of all leukaemia − Myeloid/Granulocytic (CML/CGL): All age groups − Lymphocytic (CLL): >50 years age group Acute lymphoblastic leukaemia Chronic lymphocytic leukaemia Acute leukaemia Blast cells divide but fail to differentiate and appear in blood. >20% bone marrow taken up by myeloblasts or lymphoblasts Bone marrow failure Symptoms arising from − bone marrow failure: leucopenia → infections − bone marrow infiltration: pain − other organ infiltration: e.g. brain Chronic leukaemias Usually in adults (but may be seen in children) Leukaemic cells retain ability to differentiate CLL − Commonest leukaemia, esp. in late age − Lymphocyte count > 100x109 /l − B cell proliferation − Abnormal cells in marrow, blood film, lymph nodes CML/CGL − Leucocyte count > 15x109/l − Mostly neutrophils but also myelocytes − Chromosome translocation: long arm of 22 fuses with that of 9 → Philadelphia chromosome − May transform to AML and ALL Clinical Features of chronic leukaemia Very high peripheral WBC counts Anaemia, thrombocytopenia Splenomegaly Hepatomegaly Lymphadenopathy Some with no symptoms Lymphomas The 7th commonest cancer in UK Malignant tumours of lymphoid cells; at lymph nodes or extra-nodal Classification: two main types − Hodgkin’s Lymphoma: Lymph node origin (mostly); Reed-Sternberg cells − Non-Hodgkin’s: ¾ in lymph nodes Commonly manifest by lymphadenopathy Hodgkin’s Lymphoma (HL) Peak at 3rd decade Lymphadenopathy: − rubbery/swollen lymph node (cervical, etc.) − spreads (spleen, liver, marrow, gut) Linked to previous infection with Epstein Barr virus, with a genetic predisposition Lymph node histology: Reed-Sternberg cells (multinucleate B lymphocyte) Patient presents with fever, weight loss, sweating (called B symptoms) Reed Sternberg Cell Non Hodgkin’s lymphoma (NHL) Majority of malignant lymphoma are NHL Arise in lymph nodes (eg. cervical) & spread, or extra –nodal (eg. gut) & generalised spread (eg. lungs) A wide spectrum of disease; highly proliferative or slow & indolent Most (85-90%) are B cell origin 10-15% T cell; (Follicular, Burkitts); Clinical features: − B-symptoms (fever, night sweats, weight loss) − Lymphadenopathy − extranodal presentation (GI, lung, etc.) Summary neutrophilia leucocytosis changes in numbers WBC disorders lymphocytosis leucopenia myeloid acute leukaemia lymphoid myeloid chronic neoplasm lymphoma HL NHL lymphoid Lymphocytosis occurs in which of the following conditions? a) b) c) d) e) Tissue necrosis Acute viral infection Parasitic infestation Irradiation Haemorrhage One feature of acute leukaemia is a) b) c) d) e) It only affects children Blast cells rarely appear in peripheral blood films There is no spleen enlargement Reed Sternberg cells are present in the lymph node Blast cells are accumulated in the bone marrow